Bromelain is a mixture of proteinases derived from pineapple stem. We and others have previously shown that bromelain removes cell surface molecules that affect lymphocyte migration and activation and alters the production of cytokines and inflammatory mediators by isolated leukocytes in vitro. Oral bromelain was anecdotally reported to induce remission of ulcerative colitis in two patients who were refractory to conventional medical therapy. However, the efficacy of bromelain in colitis has not yet been tested rigorously in either animals or humans. We hypothesize that bromelain can decrease the activity of inflammatory bowel disease (IBD) by proteolytically removing cell surface molecules on leukocytes and/or colonic cells that affect [unreadable] production of pro-inflammatory cytokines and chemokines. The specific aims of this study are to: 1) To [unreadable] determine the efficacy of bromelain treatment in murine models of IBD; and 2) To determine the effect of in vitro bromelain treatment on production of pro-inflammatory cytokines and chemokines by cells present in human colon biopsies. Current lack of knowledge about potential mechanisms by which bromelain therapy may modify inflammatory activity in IBD has hindered its serious consideration by mainstream medicine. The proposed studies will provide pre-clinical efficacy and mechanistic data that will be necessary for future studies of this complementary biologically-based approach to treatment of IBD. This research will thus strengthen the biomedical research knowledge base needed to inform the practice of complementary and alternative medicine. [unreadable] [unreadable]